CLOZARIL TABLET 25 MG [SIN07234P]

Product Info

CLOZARIL TABLET 25 MG

[SIN07234P]

3. INDICATIONS

3.1 Treatment-resistant schizophrenia

Clozaril is indicated in patients with treatment-resistant schizophrenia, i.e. patients with schizophrenia who are non-responsive to or intolerant of classic antipsychotics.

Non-responsiveness is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two marketed antipsychotics prescribed for adequate durations.

Intolerance is defined as the impossibility of achieving adequate clinical benefit with classic antipsychotics because of severe and untreatable neurological adverse reactions (extrapyramidal side effects or tardive dyskinesia).

4. DOSAGE AND ADMINISTRATION

4.1 Dosage information

The dosage must be adjusted individually. For each patient the lowest effective dose should be used. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation.

Initiation of Clozaril treatment must be restricted to those patients with a WBC count ≥3500/mm³ (3.5 x 10⁹/L) and an ANC ≥2000/mm³ (2.0 x 10⁹/L), and within standardized normal limits.

Dose adjustment is indicated in patients who are also receiving medicinal products that have pharmacokinetic interactions with clozapine, such as benzodiazepines or selective serotonin re-uptake inhibitors (see section INTERACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Method of administration

Clozaril is administered orally.

4.3 Switching from a previous antipsychotic therapy to Clozaril

It is generally recommended that Clozaril should not be used in combination with other antipsychotics. When Clozaril therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that the dosage of other antipsychotics be reduced or discontinued by gradually tapering it downwards. Based on the clinical circumstances, the prescribing physician should judge whether or not to discontinue the other antipsychotic therapy before initiating treatment with Clozaril.

4.4 Treatment resistant schizophrenia

4.4.1 Starting therapy

Clozaril should be started with 12.5 mg (half a 25 mg tablet) once or twice on the first day, followed by one or two 25 mg tablets on the second day. If well tolerated, the daily dose may then be increased slowly in increments of 25 mg to 50 mg in order to achieve a dose level of up to 300 mg/day within 2 to 3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50 mg to 100 mg at half-weekly or, preferably, weekly intervals.

4.4.2 Therapeutic dose range

In most patients, antipsychotic efficacy can be expected with 300 to 450 mg/day given in divided doses. Some patients may be treated with lower doses, and some patients may require doses up to 600 mg/day. The total daily dose may be divided unevenly, with the larger portion being taken at bedtime.

4.4.3 Maximum dose

To obtain full therapeutic benefit, a few patients may require larger doses, in which case judicious increments (not exceeding 100 mg) are permissible up to 900 mg/day. However the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.

4.4.4 Maintenance dose

After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses. Careful downward titration is therefore recommended. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, once daily administration in the evening may be appropriate.

4.4.5 Ending therapy

In the event of planned termination of Clozaril therapy, a gradual reduction in dose over a 1 to 2-week period is recommended. If abrupt discontinuation is necessary (e.g. because of leucopenia), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound (see section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.4.6 Restarting therapy

In patients in whom the interval since the last dose of Clozaril exceeds 2 days, treatment should be re-initiated with 12.5 mg (half a 25-mg tablet) given once or twice on the first day. If this dose is well tolerated, it may be feasible to titrate the dose to the therapeutic level more quickly than is recommended for initial treatment. However, in any patient who has previously experienced respiratory or cardiac arrest with initial dosing (see section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), but was then able to be successfully titrated to a therapeutic dose, re-titration should be done with extreme caution.

4.5 Special populations

4.5.1 Cardiovascular disorders

In patients suffering from cardiovascular disorders (note: severe cardiovascular disorders are contraindications) the initial dose should be 12.5 mg given once on the first day, and dosage increase should be slow and in small increments.

4.5.2 Renal impairment

In patients with mild to moderate renal impairment the initial dose should be 12.5 mg given once on the first day, and dosage increase should be slow and in small increments.

4.5.3 Hepatic impairment

Patients with hepatic impairment should receive Clozaril with caution along with regular monitoring of liver function tests (see section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.5.4 Pediatrics

No pediatric studies have been performed. The safety and efficacy of Clozaril in children and adolescents have not been established.

4.5.5 Patients 60 years of age and older

It is recommended that treatment in patients 60 years and older is initiated at a particularly low dose (12.5 mg given once on the first day) with subsequent dose increments restricted to 25 mg/day.

5. CONTRAINDICATIONS

• Known hypersensitivity to clozapine or to any of the excipients of Clozaril.

• Patients unable to undergo regular blood tests.

• History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of granulocytopenia/agranulocytosis from previous chemotherapy).

• Impaired bone marrow function.

• Uncontrolled epilepsy.

• Alcoholic and other toxic psychoses, drug intoxication, comatose conditions.

• Circulatory collapse and/or CNS depression of any cause.

• Severe renal or cardiac disorders (e.g. myocarditis).

• Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure.

• Paralytic ileus.

• History of Clozaril-induced agranulocytosis.